OPPORTUNITY: a randomized clinical trial of growth hormone on outcome in hemodialysis patients.
BACKGROUND
The mortality rate of maintenance hemodialysis (MHD) patients remains high. Measures of protein-energy wasting, including hypoalbuminemia, are strongly associated with their high mortality. Growth hormone (GH) may improve lean body mass (LBM) and serum albumin levels, and health-related quality of life (HRQoL), which are significantly and positively associated with survival in MHD patients. The OPPORTUNITY Trial will examine whether GH reduces mortality and morbidity and improves overall health in hypoalbuminemic MHD patients.


OBJECTIVE
The primary hypothesis is that daily recombinant human GH injections, compared with placebo, improve survival in hypoalbuminemic MHD patients. Secondary hypotheses are that GH improves morbidity and health, including number of hospitalized days, time to cardiovascular events, LBM, serum protein and inflammatory marker levels, exercise capacity, and HRQoL, and has a favorable safety profile.


METHODS
This is a prospective, double-blind, multicenter, randomized clinical trial involving 2500 MHD patients, up to 50% with diabetes mellitus, from 22 countries. Patients are randomized in a 1:1 ratio to receive daily injections of GH (20 microg/kg per day) or placebo for 104 weeks. Key inclusion criteria include clinically stable and well-dialyzed (Kt/V > or =1.2) adult MHD patients with serum albumin <4.0 g/dl. Exclusion criteria include active malignancy, active proliferative or severe nonproliferative diabetic retinopathy, uncontrolled hypertension, chronic use of high-dose glucocorticoids, or immunosuppressive agents and pregnancy.


CONCLUSIONS
The OPPORTUNITY Trial is the first large-scale randomized clinical trial in adult MHD patients evaluating the response to GH of such clinical endpoints as mortality, morbidity, markers of body protein mass, inflammation, exercise capacity, and HRQoL.
Kopple
Joel D
JD
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, David Geffen School of Medicine at UCLA, Torrance, CA 90509, USA. jkopple@labiomed.org
Cheung
Alfred K
AK
Christiansen
Jens Sandahl
JS
Djurhuus
Christian Born
CB
El Nahas
Meguid
M
Feldt-Rasmussen
Bo
B
Lange
Martin
M
Mitch
William E
WE
Wanner
Christoph
C
Wiedemann
Jonas
J
Ikizler
T Alp
TA
D000328:Adult; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D017079:Exercise Tolerance; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D034141:Hypoalbuminemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000401:mortality; D018836:Inflammation Mediators / Q000097:blood; D007267:Injections; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D008297:Male; D011446:Prospective Studies; D011788:Quality of Life; D011994:Recombinant Proteins / Q000008:administration & dosage; D006435:Renal Dialysis / Q000401:mortality; D012107:Research Design; D012709:Serum Albumin / Q000378:metabolism; D016896:Treatment Outcome
D015415:Biomarkers; D018836:Inflammation Mediators; D011994:Recombinant Proteins; D012709:Serum Albumin; D019382:Human Growth Hormone